NCT02624817

Brief Summary

The purpose of this study is to investigate long term response of sulfonylurea and glucose control in children with diabetes due to mutations in KCNJ11 that have been switched from insulin injections to sulfonylurea tablets.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Dec 2015

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2015

Completed
3 days until next milestone

First Submitted

Initial submission to the registry

December 4, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 8, 2015

Completed
8 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

October 3, 2017

Status Verified

September 1, 2017

Enrollment Period

8 months

First QC Date

December 4, 2015

Last Update Submit

September 29, 2017

Conditions

Permanent Neonatal Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

  • Sulfonylurea efficacy

    Insulin requirement with or without sulfonylurea treatment during the intervention

    Within 13 years from intervention

  • Metabolic control

    Change in HbA1c levels during the intervention

    Within 13 years from intervention

Secondary Outcomes (9)

  • All cause mortality

    Within 13 years from intervention

  • Incidence of hypoglycemia

    Within 13 years from intervention

  • Incidence of ketoacidosis

    Within 13 years from intervention

  • Development of diarrhea

    Within 13 years from intervention

  • Development of discoloured teeth

    Within 13 years from intervention

  • +4 more secondary outcomes

Study Arms (1)

Drug: Sulfonylurea

EXPERIMENTAL

Sulfonylurea tablets (glibenclamide, other forms of sulfonylureas) were administered at the time of intervention (before November 1, 2006). The patients have been prospectively followed up. Sulfonylurea dose, insulin requirement, death of all causes, episodes of severe hypoglycemia, ketoacidosis, development of discoloured teeth and diarrhea have been recorded. For a small number of subjects, increment of insulin and C-peptide after either an oral or intravenous glucose load and/or response to glucagon have been tested.

Drug: Sulfonylurea

Interventions

SulfonylureaDRUG

See Arm description.

Also known as: Glibenclamide and other forms of sulfonylureas
Drug: Sulfonylurea

Eligibility Criteria

Age9 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Permanent diabetes due to a mutation in KCNJ11 (KIR6.2)
  • Patients successfully transferred from insulin to sulfonylurea
  • Transferred to sulfonylurea treatment before November 1, 2006 (ie 9 years off insulin)
  • Willing and able to provide informed consent (parents if younger than 16 years of age)

You may not qualify if:

  • Permanent diabetes not due to a mutation in KCNJ11 (KIR6.2)
  • Patients not successfully transferred from insulin to sulfonylurea
  • Transferred to sulfonylurea treatment after November 1, 2006 (ie less than 9 years off insulin)
  • Not willing or able to provide informed consent (parents if younger than 16 years of age)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Haukeland University Hospital

Bergen, 5021, Norway

Location

Related Publications (9)

  • Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njolstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004 Apr 29;350(18):1838-49. doi: 10.1056/NEJMoa032922.

    PMID: 15115830RESULT

  • Sagen JV, Raeder H, Hathout E, Shehadeh N, Gudmundsson K, Baevre H, Abuelo D, Phornphutkul C, Molnes J, Bell GI, Gloyn AL, Hattersley AT, Molven A, Sovik O, Njolstad PR. Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes. 2004 Oct;53(10):2713-8. doi: 10.2337/diabetes.53.10.2713.

    PMID: 15448106RESULT

  • Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Sovik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. doi: 10.1056/NEJMoa061759.

    PMID: 16885550RESULT

  • Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT; Neonatal Diabetes International Collaborative Group. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008 Feb;31(2):204-9. doi: 10.2337/dc07-1785. Epub 2007 Nov 19.

    PMID: 18025408RESULT

  • Stoffers DA, Zinkin NT, Stanojevic V, Clarke WL, Habener JF. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet. 1997 Jan;15(1):106-10. doi: 10.1038/ng0197-106.

    PMID: 8988180RESULT

  • Njolstad PR, Sovik O, Cuesta-Munoz A, Bjorkhaug L, Massa O, Barbetti F, Undlien DE, Shiota C, Magnuson MA, Molven A, Matschinsky FM, Bell GI. Neonatal diabetes mellitus due to complete glucokinase deficiency. N Engl J Med. 2001 May 24;344(21):1588-92. doi: 10.1056/NEJM200105243442104. No abstract available.

    PMID: 11372010RESULT

  • Babenko AP, Polak M, Cave H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006 Aug 3;355(5):456-66. doi: 10.1056/NEJMoa055068.

    PMID: 16885549RESULT

  • Svalastoga P, Sulen A, Fehn JR, Aukland SM, Irgens H, Sirnes E, Fevang SKE, Valen E, Elgen IB, Njolstad PR. Intellectual Disability in KATP Channel Neonatal Diabetes. Diabetes Care. 2020 Mar;43(3):526-533. doi: 10.2337/dc19-1013. Epub 2020 Jan 13.

    PMID: 31932458DERIVED

  • Bowman P, Sulen A, Barbetti F, Beltrand J, Svalastoga P, Codner E, Tessmann EH, Juliusson PB, Skrivarhaug T, Pearson ER, Flanagan SE, Babiker T, Thomas NJ, Shepherd MH, Ellard S, Klimes I, Szopa M, Polak M, Iafusco D, Hattersley AT, Njolstad PR; Neonatal Diabetes International Collaborative Group. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018 Aug;6(8):637-646. doi: 10.1016/S2213-8587(18)30106-2. Epub 2018 Jun 4.

    PMID: 29880308DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Permanent Neonatal

Interventions

Sulfonylurea CompoundsGlyburide

Intervention Hierarchy (Ancestors)

UreaAmidesOrganic ChemicalsSulfonesSulfur Compounds

Study Officials

  • Pål R Njølstad, MD PhD

    Haukeland University Hospital

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 4, 2015

First Posted

December 8, 2015

Study Start

December 1, 2015

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

October 3, 2017

Record last verified: 2017-09

Locations

NO(1)